Non-alcoholic Fatty Liver Disease and Cardiovascular Disease in Hispanics/Latinos

西班牙裔/拉丁裔的非酒精性脂肪肝和心血管疾病

• 批准号: 10002271
• 负责人: JORGE R KIZER
• 金额: $ 230.38万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002271
• 关键词: 3-Dimensional; Abdomen; Acculturation; Address; Adipose tissue; Affect; Antithrombins; Assimilations; Attenuated; Behavioral; Biopsy; Cardiac; Cardiomyopathies; Cardiovascular Diseases; Cardiovascular system; Chronic stress; Cicatrix; Cirrhosis; Clinical; Data; Diabetes Mellitus; Diagnosis; Diffuse; Disease; Dominican; Endothelium; Environmental Risk Factor; Ethnic group; Evaluation; Exhibits; Factor VIII; Fatty Liver; Fatty acid glycerol esters; Functional disorder; Funding; Gene Frequency; Generations; Genetic; Genetic Predisposition to Disease; Genotype; Habits; Health; Heart; Heart Abnormalities; Heart Diseases; Heart Hypertrophy; Heart failure; Hepatic; High Prevalence; Hispanic Community Health Study/Study of Latinos; Hispanics; Imaging Techniques; Immigration; Inflammatory; Insulin Resistance; Iron; Knowledge; Latino; Life Style; Link; Lipids; Liver; Liver Fibrosis; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Malignant neoplasm of liver; Measures; Mediation; Mexican; Multi-Ethnic Study of Atherosclerosis; Myocardial; Myocardial dysfunction; Nature; Not Hispanic or Latino; Obesity; Pathogenesis; Pathway interactions; Phenotype; Policies; Population Study; Predisposition; Prevalence; Prevention approach; Puerto Rican; Reporting; Resources; Risk; Risk Factors; Role; South American; Stress; Structure; Study of Latinos; Testing; Thrombin; Time; Tissues; Variant; Visceral; Visceral fat; Visit; Vulnerable Populations; Women’s Interagency HIV Study; abdominal fat; adiponectin; cohort; coronary fibrosis; emotional distress; ethnic diversity; ethnic minority population; falls; genetic variant; heart imaging; high risk; improved; insight; liver biopsy; liver imaging; liver transplantation; low socioeconomic status; mortality; multimodality; non-alcoholic fatty liver disease; non-genetic; nonalcoholic steatohepatitis; protective factors; psychosocial; residence; response; social; social culture; socioeconomics

PROJECT SUMMARY/ABSTRACT Hispanics/Latinos (H/L) are the largest minority ethnic group in the US. Despite low socioeconomic status, H/L have lower mortality than non-Hispanic whites (NHW) – the “Hispanic Paradox.” This survival advantage declines with time and generation, which has led to the proposition that erosion of healthful lifestyle habits and social resources combine with the cumulative stresses of immigration to degrade health. Longitudinal studies examining these factors are lacking. At the same time, there is evidence that the Hispanic Paradox may not apply to major diseases. H/L suffer a high burden of non-alcoholic fatty liver disease (NAFLD), including its more advanced form, non-alcoholic steatohepatitis (NASH), which is becoming the most common cause of liver transplant in the US. NASH has been difficult to study, however, because the diagnosis has depended on biopsy. While H/L also have a disproportionate burden of obesity and diabetes, this does not fully account for NAFLD. Meanwhile, discovery of two major genetic variants that interfere with hepatic lipid processing, but do not predispose to obesity or insulin resistance, has introduced the concept of “genetic NAFLD.” This may be of particular relevance to H/L, because one such variant is highly prevalent in various H/L heritage groups. Unlike NAFLD, prevalence of CVD is lower in H/L than NHW, but cardiac dysfunction and heart failure risk appear higher. Data from our group using partial MRI of the liver has linked hepatic fibrosis to myocardial fibrosis. Here we will parlay the opportunity for a third exam of the Hispanic Community Health Study/Study of Latinos (SOL), and the strengths of contrast MRI, to address important knowledge gaps in this diverse group. We plan to evaluate relations of nativity and duration of US residence with MRI-determined hepatic fibrosis and myocardial strain, while leveraging longitudinal assessments of lifestyle, psychosocial and sociocultural factors to assess their cumulative impact on these phenotypes, and to explore mediation of immigration and acculturation effects. We will also examine the contributions of visceral fat and low adiponectin levels, as well as genetic susceptibility, alone and in combination, to hepatic fibrosis. Last, we will evaluate the association between hepatic fibrosis and myocardial fibrosis, along with proinflammatory and procoagulant factors that may link the two disorders. This study will yield key insights into the Hispanic Paradox in NAFLD and CVD and their behavioral and psychosocial determinants; newly characterize the burden of hepatic fibrosis in H/L and its genetic underpinnings; and investigate the liver-heart axis and underlying pathways as a potentially serious threat to the health of this vulnerable ethnic group.

项目概要/摘要 西班牙裔/拉丁裔 (H/L) 是美国最大的少数族裔群体，尽管社会经济地位较低，但 H/L 仍是美国最大的少数族裔群体。 死亡率低于非西班牙裔白人 (NHW)——“西班牙裔悖论”。 随着时间和世代的推移，这导致了这样的主张：健康的生活习惯和社会受到侵蚀 资源与移民的累积压力相结合，导致健康状况恶化。 同时，有证据表明西班牙裔悖论可能并不存在。 适用于H/L患有高负担的非酒精性脂肪肝病（NAFLD），包括其更多。 晚期非酒精性脂肪性肝炎 (NASH)，它正成为肝脏最常见的病因 然而，在美国，NASH 的移植研究一直很困难，因为诊断依赖于活检。 虽然 H/L 还承受着不成比例的肥胖和糖尿病负担，但这并不能完全解释 NAFLD。 同时，发现了两种主要的遗传变异，它们干扰肝脏处理脂质，但不影响肝脏处理脂质。 易患肥胖或胰岛素抵抗，引入了“遗传性 NAFLD”的概念。 与 H/L 特别相关，因为这样的一种变体在各种 H/L 遗产群体中非常普遍。 H/L 人群中 NAFLD、CVD 患病率低于 NHW，但出现心功能不全和心力衰竭风险 我们小组使用部分肝脏 MRI 得出的数据表明，肝纤维化与心肌纤维化有关。 我们将利用西班牙社区健康研究/拉丁裔研究 (SOL) 第三次考试的机会， 以及对比 MRI 的优势，以解决这个多元化群体中的重要知识差距。 评估出生和美国居住时间与 MRI 确定的肝纤维化和心肌的关系 压力，同时利用生活方式、社会和社会文化因素的纵向评估来评估 它们对这些表型的累积影响，并探索移民和文化适应效应的中介。 我们还将检查内脏脂肪和低脂联素水平以及遗传易感性的贡献， 最后，我们将评估肝纤维化与肝纤维化之间的关联。 心肌纤维化，以及可能与这两种疾病相关的促炎和促凝血因子。 研究将对 NAFLD 和 CVD 中的西班牙裔悖论及其行为和心理社会产生重要见解 决定因素；新描述 H/L 肝纤维化的负担及其遗传基础； 研究肝心轴和​​潜在的通路是否对其健康构成潜在的严重威胁 弱势族群。